The general objective is to utilize genetic markers to investigate the cause and pathogenesis of human tumors. The primary approach involves determining the number of cells from which tumors arise, thereby providing important clues to their mode of origin. For example, a neoplasm that results from a rare event, like "spontaneous" somatic mutation, would be expected to arise in a single cell. This problem is investigated in subjects with at least two genetically distinct types of cells. Tumors with clonal origin contain only one cell type, whereas both types would be more likely in neoplasms arising in several cells. X-chromosome inactivation mosaicism in females heterozygous for the glucose-6-phosphate dehydrogenase (G-6-PD) locus is used to provide data relevant to the following questions which have important therapeutic implications: 1. Do the myeloproliferative disorders and leukemias have single or multiple cell origin? 2. Do they originate in pluripotent stem cells or more differentiated progenitors? 3. Are there residual normal stem cells in patients with hematopoietic neoplasms? 4. Do tumors which occur in syndromes clearly inherited by mendelian mechanisms have multicellular origin? 5. Do neoplasms with strong environmental influences (e.g., viral and endocrine tumors) have multicellular origin? 6. Does the pathogenesis of embryonal tumors and other cancers involve sequential mutations?